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Introduction: It has been suggested that uncontrolled epilepsy might not necessarily equate to drug resistance when antiepileptic drugs (AEDs) are used at relatively low doses, a practice frequently observed in rural areas of China.Objective: To assess the clinical benefits of further drug manipulation in this situation, we prospectively followed up the outcomes of patients with uncontrolled epilepsy while taking relatively low doses of AEDs.Methods: The study included patients aged 16 years and older with uncontrolled epilepsy and who were receiving at least one AED at a dosage below 50% of the World Health Organization (WHO) defined daily dose (DDD) (50% DDD) (Group 1). Patients with drug-resistant epilepsy were included for comparison (Group 2). Both groups were followed-up for at least 2 years. Seizure outcomes after further drug manipulations were recorded at the last follow-up.Results: A total of 197 patients (55.3% male) were included in Group 1 and 32 (46.9% male) in Group 2; their mean duration of follow-up was 28.85 ± 1.90 and 30.91 ± 2.04 months, respectively. At the last follow-up, 16.8% (33/197) of patients in Group 1 had become seizure-free compared with none in Group 2 (p < 0.001). Seventeen of 93 (18.3%) patients in Group 1 became seizure free after increasing the dosage of baseline AED(s) alone. Only 5.5% (3/55) of patients who had failed to respond to an AED at ≥50% DDD at baseline became seizure free compared with 21.1% (30/142) who did not have such a history (p = 0.001). The number of AEDs taken at a dosage below 50% DDD at baseline was not associated with seizure outcome.Conclusions: Uncontrolled epilepsy could become controlled in a substantial proportion of patients by dose increase alone, particularly if there is no history of drug failure at ≥50% DDD. [ABSTRACT FROM AUTHOR]